An investigation of downstream processing methods for challenging skeletal samples.

While skeletal remains are known for their resilience and often serve as the final source of information for unidentified human remains (UHRs), the traditional downstream processing of these samples is challenging due to their low template nature, DNA degradation, and the presence of PCR inhibitors, typically resulting in limited probative information. To address this issue, advanced genotyping methods can be explored to retrieve additional genetic information from these challenging samples to maximize investigative leads. Therefore, this study investigated the effectiveness of three advanced genotyping methods and assessed their suitability with compromised skeletal samples: 1) targeted next generation sequencing (NGS) of both STRs and SNPs using the ForenSeq® DNA Signature Prep chemistry, 2) targeted NGS of SNPs using the ForenSeq® Kintelligence kit, and 3) SNP genotyping using a microarray via the Infinium Global Screening Array.

Gold Nanoparticle Detection with Two-Photon Excitation Fluorescence Lifetime Imaging of NAD(P)H in Cancer Cells: An Analytical Approach to Separate Nanoparticle and NAD(P)H Signals.

Gold nanoparticles (AuNPs) have shown promise for applications in the diagnosis and treatment of different diseases, including cancer. Understanding the effect of AuNPs on metabolic reprogramming in cancer cells at the single cell level is of high importance for improving the efficacy and safety. Fluorescence lifetime imaging microscopy (FLIM) of nicotinamide adenine dinucleotide (phosphate) hydrogen (NAD(P)H) as a main metabolic cofactor and an indicator of metabolic reprogramming in cancer cells enables real-time monitoring of cancer cell metabolism in response to different treatments, including AuNPs.

PAMAM dendrimers as mediators of dermal and transdermal drug delivery: a review.

Objectives: Poly(amidoamine) dendrimers have been widely investigated as potential nanomaterials that can enhance the skin permeation of topically applied drugs. This article reviews the studies that have used dendrimers as penetration enhancers and examines the mechanisms by which enhancement is claimed.

Key Findings: A wide range of studies have demonstrated that, in certain circumstances and for certain drugs, the incorporation of dendrimers into a topically applied formulation can significantly increase the amount of drug passing into and through the skin.

A Review of Medication Errors and the Second Victim in Pediatric Pharmacy.

The concept of the second victim, described as the sense of victimization of health care professionals following the exposure to a traumatic, unanticipated medical error, was first introduced in 2000 by Albert W. Wu. Since then, the concept has gained immense traction and inspired the generation of assistance programs for second victims.

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Innovative Topical Patches for Non-Melanoma Skin Cancer: Current Challenges and Key Formulation Considerations.

Non-melanoma skin cancer (NMSC) is the most prevalent malignancy worldwide, with approximately 6.3 million new cases worldwide in 2019. One of the key management strategies for NMSC is a topical treatment usually utilised for localised and early-stage disease owing to its non-invasive nature.

Paternal Leave Entitlement and Workplace Culture: A Key Challenge to Paternal Mental Health.

Paternal mental health continues to be a health concern in the UK. Paternal leave entitlement and workplace cultures have failed to support fathers in navigating the complexity of fatherhood, which has an impact on fathers' wellbeing. Interviewing twenty fathers in the York area, this study seeks to explore the impact of parental leave entitlements and workplace cultures on fathers' mental health.

Considerations for Treating Nonobstetric Diseases in Pregnant Patients in the Emergency Department Setting.

Objective: To provide nonobstetric practitioners with an overview of key concepts for the pregnant patient and review treatment of 3 common acute nonobstetric diseases encountered in the emergency department setting.

Data Sources: A literature search of PubMed was performed (1997-February 2023) using key search terms related to pregnancy, pain, urinary tract infection (UTI), venous thromboembolism (VTE), and anticoagulants.

Study Selection And Data Extraction: Relevant articles in English and humans were considered.

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach.

Background: Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option.

Methods: Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach.

Seborrheic dermatitis: topical therapeutics and formulation design.

Seborrheic dermatitis (SD) is a common dermatological disorder with symptoms that include skin flaking, erythema and pruritus. This review discusses the topical products available for treating SD, which target several aspects of disease pathobiology, including cutaneous microbial dysbiosis (driven by Malassezia yeast), inflammation, sebum production and skin barrier disruption. Among the various treatments available, zinc pyrithione (ZnPT) based products that exhibit anti-fungal action are the market leaders.

The effectiveness of various strategies to improve DNA analysis of formaldehyde-damaged tissues from embalmed cadavers for human identification purposes.

Formalin-fixed tissues provide the medical and forensic communities with alternative and often last resort sources of DNA for identification or diagnostic purposes. The DNA in these samples can be highly degraded and chemically damaged, making downstream genotyping using short tandem repeats (STRs) challenging. Therefore, the use of alternative genetic markers, methods that pre-amplify the low amount of good quality DNA present, or methods that repair the damaged DNA template may provide more probative genetic information.

Examining the Relationship between Paternal Mental Health and Informal Support Networks: Reflections on the Impact of the COVID-19 Pandemic.

Paternal mental health remains an under-researched area in the UK. Consequently, father-focused formal and informal support provisions fail to address the complex emotional and psychological wellbeing needs of fathers. Drawing on data from twenty semi-structured interviews with fathers in the York area, this study seeks to better understand how access to and participation in informal support networks is influenced by gendered perceptions and the impact hegemonic perceptions of masculinity have on fathers' access to support prior and during the COVID-19 pandemic.

Human epidermal in vitro permeation test (IVPT) analyses of alcohols and steroids.

This study examined a number of factors that can impact the outcomes of in vitro human epidermal permeation coefficients for aliphatic alcohols and steroids, including receptor phase composition and study conditions. We determined experimentally the solubilities and IVPT permeation of a homologous series of C labeled aliphatic alcohols (ethanol, propanol, pentanol, heptanol, octanol and decanol) in different receptor fluids as recommended by Organisation Economic Co-operation and Development (OECD). We used human epidermal membranes at 25 °C and phosphate-buffered saline (PBS), 2 %w/v bovine serum albumin (2 %w/v BSA), 50 %w/v ethanol and 0.

Multi-Modal Imaging to Assess the Follicular Delivery of Zinc Pyrithione.

Zinc pyrithione (ZnPT) is a widely used antifungal, usually applied as a microparticle suspension to facilitate delivery into the hair follicles, where it then dissociates into a soluble monomeric form that is bioactive against yeast and other microorganisms. In this study, we use multiphoton microscopy (MPM) and fluorescence lifetime imaging microscopy (FLIM) to characterise ZnPT formulations and map the delivery of particles into follicles within human skin. To simulate real-world conditions, it was applied using a massage or no-massage technique, while simultaneously assessing the dissolution using Zinpyr-1, a zinc labile fluorescent probe.

Advances and future perspectives in epithelial drug delivery.

Epithelial surfaces protect exposed tissues in the body against intrusion of foreign materials, including xenobiotics, pollen and microbiota. The relative permeability of the various epithelia reflects their extent of exposure to the external environment and is in the ranking: intestinal≈ nasal ≥ bronchial ≥ tracheal > vaginal ≥ rectal > blood-perilymph barrier (otic), corneal > buccal > skin. Each epithelium also varies in their morphology, biochemistry, physiology, immunology and external fluid in line with their function.

Review of direct PCR and Rapid DNA approaches to streamline sexual assault kit testing.

Crime laboratories have been faced with large casework backlogs due to lengthy processing times, limited resources and scientists, and rising crime rates. Evidence related to sexual assault crimes, specifically sexual assault kits (SAKs), heavily contribute to the reported backlogs. Although more sensitive, faster chemistries and automated techniques have been implemented over the years, the traditional STR workflow remains relatively unchanged.

Comparison of Two Morphine Dosing Strategies in the Management of Neonatal Abstinence Syndrome.

Objective: The incidence of neonatal abstinence syndrome (NAS) has increased in recent years. Treatment approaches usually involve opioid replacement; however, the optimal treatment strategy is unknown. This study sought to determine the impact of weight- and symptom-based morphine dosing strategies on LOS and medication exposure in patients with NAS.

Human Epidermal Zinc Concentrations after Topical Application of ZnO Nanoparticles in Sunscreens.

Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (Zn) ZnO NP sunscreen applied to excised human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing, and a laser-ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) methodology.

Awareness of developmental language disorder amongst workplace managers.

Background: Developmental Language Disorder (DLD) is one of the most prevalent developmental disorders and affects expressive and receptive language with no clear cause (Bishop et al., 2017). Awareness of DLD is currently much lower than other (sometimes less prevalent) disorders such as Autism or Attention Deficit Hyperactivity Disorder (ADHD) (Bishop, 2010).

Evolution of biofilm-forming pathogenic bacteria in the presence of nanoparticles and antibiotic: adaptation phenomena and cross-resistance.

Background: Treatment of bacterial biofilms are difficult and in many cases, expensive. Bacterial biofilms are naturally more resilient to antimicrobial agents than their free-living planktonic counterparts, rendering the community growth harder to control. The present work described the risks of long-term use of an important alternative antimicrobial, silver nanoparticles (NAg), for the first time, on the dominant mode of bacterial growth.

Targeted Delivery of Zinc Pyrithione to Skin Epithelia.

Zinc pyrithione (ZnPT) is an anti-fungal drug delivered as a microparticle to skin epithelia. It is one of the most widely used ingredients worldwide in medicated shampoo for treating dandruff and seborrheic dermatitis (SD), a disorder with symptoms that include skin flaking, erythema and pruritus. SD is a multi-factorial disease driven by microbiol dysbiosis, primarily involving yeast.

The performance of quality controls in the Investigator® Quantiplex® Pro RGQ and Investigator® 24plex STR kits with a variety of forensic samples.

Forensic DNA laboratories process database reference samples on FTA® cards or buccal swabs, which commonly contain adequate amounts of quality DNA resulting in full STR profiles and high first-pass rates. However, some reference samples and many forensic casework samples are exposed to a variety of insults that may lead to low quantities of DNA, DNA degradation, DNA mixtures, and/or PCR inhibition, posing a challenge to downstream genotyping success. The inclusion of multiple amplification targets and internal PCR controls (IPCs) in DNA quantification kits, and quality sensors within STR amplification kits can aid in the accurate interpretation of sample/profile quality, and guide more efficient rework strategies when needed.

Topical drug delivery: History, percutaneous absorption, and product development.

Topical products, widely used to manage skin conditions, have evolved from simple potions to sophisticated delivery systems. Their development has been facilitated by advances in percutaneous absorption and product design based on an increasingly mechanistic understanding of drug-product-skin interactions, associated experiments, and a quality-by-design framework. Topical drug delivery involves drug transport from a product on the skin to a local target site and then clearance by diffusion, metabolism, and the dermal circulation to the rest of the body and deeper tissues.

Using buprenorphine to treat neonatal abstinence syndrome: a quality improvement study.

Objective: To assess if treating neonatal abstinence syndrome (NAS) with sublingual buprenorphine (SLB) would decrease the mean duration of therapy (DOT) and length of birth hospital stay (LOS).

Study Design: Conducted at a tertiary hospital with >6000 annual deliveries and a 2% incidence of NAS, a quality improvement study using plan-do-study-act (PDSA) cycles were utilized. Outcomes were measured using statistical process control (SPC) charts.

Comparison of neonatal outcomes with use of a soybean oil-based injectable lipid emulsion vs a 4-oil emulsion product.

Purpose: Results of a study comparing the safety and efficacy outcomes with use of a soybean oil-based injectable lipid emulsion (SO-ILE) vs a 4-oil alternative product in a neonatal population are presented.

Methods: In an institutional review board-approved, multicenter retrospective review, the medical records of 328 patients who were born at a gestational age of ≤34 weeks, had a birth weight of 500 to 2,000 g, were admitted to one of 2 neonatal intensive care units (NICUs) within a large health system, and received at least 7 days of a parenteral nutrition containing either lipid emulsion product were reviewed: 151 (46%) had received SO-ILE and 177 (54%) had received SMOFlipid (Fresenius Kabi). The primary outcome of the study was a composite of development of cholestasis and development of hypertriglyceridemia.